Membrane changes that occur in the course of neoplastic transformation will be defined in molecular terms and will be correlated with membrane and cell surface expressions relative to differentiation and degree of malignancy. Special attention will be focused on the role of lysophosphatidylcholine (lysoPC) and other lysoPC-type choline phospholipids derived from short-chain diols, in various membrane, enzyme and cell processes. The controlling steps in maintaining physiological levels of these monochain choline phospholipids will be established. The effects of lysoPC and diol-derived phosphocholines will be studied in cultured Novikoff rat hepatoma cells and in tumors grown in rodents, virally transformed BALB/3T3 cells and cells from human tumors, as well as in respective controls. The effect of drug-induced lysoPC stimulation on membrane transport, including choline and chlorambucil uptake, will be followed. Changes in membrane phospholipid metabolism during virus-induced neoplastic transformation, particularly at the time of virus entry, will be investigated. The effect of monochain choline phospholipids on membrane and surface properties of normal and transformed cells will be defined in terms of their susceptibility to lysis and in terms of membrane fluidity as expressed by nuclear magnetic resonance parameters. Monochain choline phospholipid-cholesterol-lecithin interactions will be studied in model membranes and tumor cells. Drug-mediated lysolecithin stimulation will be evaluated as a means of modulating cell surface behavior and of possibly influencing cancerous proliferation. The effect of membrane cholesterol levels of neoplastic cells on their susceptibility to lysis, on their ability to metastasize and on their resistance to immune attack will be further investigated.